In an attempt to study the mechanisms leading to fibrosis in chronic pancreatitis, an in situ immunohistochemical investigation of lymphocytes and of class II major histocompatibility complex expression (HLA-DR) by epithelial cells has been designed. Samples of normal pancreas (n = 8), chronic calcifying pancreatitis (n = 4), chronic obstructive pancreatitis (n = 6), and diffuse fibrosing pancreatitis (n = 6) have been studied. In normal pancreas, T-lymphocytes were rare and were located in the epithelial layer of pancreatic ducts and in the periductal connective tissue. Duct cells were constantly HLA-DR negative. In chronic calcifying pancreatitis and chronic obstructive pancreatitis, T cells were numerous and were located around ducts and in the spreading areas of fibrous septa. In chronic obstructive pancreatitis, the duct cells strongly expressed the HLA-DR antigen. In diffuse fibrosing pancreatitis, fibrous tissue was devoid of lymphocytes and duct cells never expressed the HLA class II antigen. These results suggest that lymphocytes are involved in the fibrosing process occurring in chronic calcifying pancreatitis and chronic obstructive pancreatitis but not in diffuse fibrosing pancreatitis. The significance of de novo expression of HLA-DR antigen by duct cells is discussed.